Department of Neurobiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, People's Republic of China.
Hippocampus. 2014 Jan;24(1):44-53. doi: 10.1002/hipo.22202. Epub 2013 Sep 30.
Rattin, a specific derivative of humanin in rats, shares the ability with HN to protect neurons against amyloid β (Aβ) peptide-induced cellular toxicity. However, it is still unclear whether Rattin can protect against Aβ-induced deficits in cognition and synaptic plasticity in rats. In the present study, we observed the effects of Rattin and Aβ31-35 on the spatial reference memory and in vivo hippocampal Long-term potentiation of rats by using Morris water maze test and hippocampal field potential recording. Furthermore, the probable molecular mechanism underlying the neuroprotective roles of Rattin was investigated. We showed that intra-hippocampal injection of Rattin effectively prevented the Aβ31-35-induced spatial memory deficits and hippocampal LTP suppression in rats; the Aβ31-35-induced activation of Caspase-3 and inhibition of STAT3 in the hippocampus were also prevented by Rattin treatment. These findings indicate that Rattin treatment can protect spatial memory and synaptic plasticity of rats against Aβ31-35-induced impairments, and the underlying protective mechanism of Rattin may be involved in STAT3 and Caspases-3 pathways. Therefore, application of Rattin or activation of its signaling pathways in the brain might be beneficial to the prevention of Aβ-related cognitive deficits.
Rattin 是大鼠中与人神经保护因子(HN)具有同源性的一种特定衍生物,它与 HN 具有相同的能力,能够保护神经元免受淀粉样β肽(Aβ)诱导的细胞毒性。然而,目前尚不清楚 Rattin 是否能防止 Aβ 诱导的大鼠认知和突触可塑性缺陷。在本研究中,我们通过 Morris 水迷宫测试和海马场电位记录,观察了 Rattin 和 Aβ31-35 对大鼠空间参考记忆和体内海马长时程增强的影响。此外,还研究了 Rattin 发挥神经保护作用的可能分子机制。结果表明,海马内注射 Rattin 可有效预防 Aβ31-35 诱导的大鼠空间记忆缺陷和海马 LTP 抑制;Rattin 处理还可预防 Aβ31-35 诱导的海马 Caspase-3 激活和 STAT3 抑制。这些发现表明,Rattin 治疗可防止 Aβ31-35 诱导的大鼠空间记忆和突触可塑性损伤,Rattin 的潜在保护机制可能涉及 STAT3 和 Caspases-3 途径。因此,在大脑中应用 Rattin 或激活其信号通路可能有益于预防与 Aβ 相关的认知缺陷。